Mustafa Altinbas

Frequency of flutamide induced hepatotoxicity in patients with prostate carcinoma

To identify and describe the frequency and severity of hepatotoxicity in patients who received flutamide therapy for prostate cancer, 22 patients were treated with the combination of flutamide and goserilin or orchiectomy. After diagnosis and staging of prostate cancer, baseline results were obtained for a set of five liver function tests (LF Ts). Hepatotoxicity was assessed according to the WHO criteria. After initiation of flutamide therapy, LF Ts were performed at 4, 8 and 12 weeks and every 2 months thereafter. Severe hepatotoxicity appeared in two of 22 (9%) patients. Following the discontinuation of flutamide, one patient died due to acute liver failure. On the other patient an improvement of LF Ts occurred after cessation of flutamide. The observed severe hepatotoxicity in two of 22 (9%) patients occurred more frequent than is predicted in the literature. Patients treated with flutamide, having symptomatic or asymptomatic liver enzyme elevations, should be taken off therapy as soon as possible.

Rapidly Relapsing Squamous Cell Carcinoma of the Renal Pelvis Associated with Paraneoplastic Syndromes of Leukocytosis, Thrombocytosis and Hypercalcemia

A case history is reported here in which leukocytosis, thrombocytosis and hypercalcemia associated with rapidly relapsing squamous cell carcinoma (SCC) of the renal pelvis were observed. In a 58-year-old man, SCC of the renal pelvis was documented during nephrolithotomy, and right nephrectomy was performed. Local relapse of the tumor occurred rapidly in 2 months’ time and hypercalcemia, leukocytosis and thrombocytosis worsened in accordance with tumor volume. Cranial computerized tomography (CT), thorax CT and bone scintigraphy were negative for metastasis. The serum parathyroid hormone level was 28 pg/ml (normal 9– 55 pg/ml). To disclose leukocytosis and thrombocytosis, peripheral smear and bone marrow aspiration were performed and no pathologic finding regarding any hematologic disorder was found; the samples were also BCR-ABL negative and Philadelphia chromosome negative. Production of several factors by tumor cells may be responsible for this paraneoplastic syndrome. The association of SCC of the renal pelvis with this triple paraneoplastic syndrome is an extremely rare occurrence.

High prevalence of diabetes in patients with pancreatic cancer in central Anatolia, Turkey

Tumor-induced pancreatic damage or insulin resistance may be responsible for diabetes in pancreatic cancer (PC) patients, but the exact cause of association remains controversial. In this study, we aimed to investigate the prevalence of diabetes in patients with PC in central Anatolia, Turkey, and to evaluate whether diabetes is caused by PC. A total of 40 patients with primary PC were enrolled in the study. 13 (32.5%) of the patients had diabetes before PC diagnosis. Oral glucose tolerance test was performed in the remaining 27 patients. The period between the diagnosis of diabetes and detection of PC was less than 1 year in seven (17.5%) patients who had previous diabetes. Recent-onset diabetes and impaired glucose tolerance were detected in 13 (32.5%) and two (5%) of the PC patients, respectively. The prevalence of recent-onset and shortly-before-diagnosed diabetes has been found very high (50%) in our patients with PC. Interestingly, we determined higher levels of insulin and C-peptide in PC patients having abnormal glucose tolerance than patients having normal glucose tolerance. In conclusion, as it has been reported in other population, we determined high prevalence of diabetes in PC patients in central Anatolia. High insulin and C-peptide level indicate that different mechanisms such as insulin resistance may be responsible for abnormal glucose tolerance in PC patients other than the tumor caused insulin deficiency.

Inhibition of Angiogenesis: Thalidomide or Low-Molecular-Weight Heparin?

TO THE EDITOR: In the July 15, 2004, issue of the Journal of Clinical Oncology, Dahut et al showed that the addition of thalidomide to docetaxel resulted in an encouraging prostatespecific antigen decline and overall median survival rate in patients with metastatic androgen-independent prostate cancer. In this study, low-molecular-weight heparin (LMWH) was offered to patients in the combination arm for median 6 months, but not offered to patients in the control arm. Preclinical evidence suggests that angiogenesis is important for tumor progression in prostate cancer. LMWH inhibits angiogenesis, and this effect seems to be independent of the anticoagulant actions. In a recent randomized study, we tested the effect on patient mortality of a prophylactic dose of LMWH (dalteparin; 5,000 U/d subcutaneously) given in combination with chemotherapy versus chemotherapy alone in patients with small-cell lung cancer (42 patients per group). This trial demonstrated an improvement in overall survival for those patients randomly assigned to receive LMWH. In another recent randomized study, the FAMOUS (Fragmin Advanced Malignancy Outcome Study) Trial, 385 patients with advanced solid cancers were randomly assigned to receive a prophylactic dose of the dalteparin or placebo for up to 1 year. There was suggestion of a marked survival advantage for patients with a better prognosis receiving LMWH therapy. We think that LMWH could provide a therapeutic and survival advantage for patients in the thalidomide arm in the Dahut et al study. To understand whether this survival advantage is depending on thalidomide, the authors should have used LMWH on the control arm as well.

Antiphospholipid Syndrome Associated with Malignant Mesothelioma Presenting with Superior Vena Cava Thrombosis: A Case Report

A 59-year-old woman who had dyspnea and neck swelling for 10 days was admitted to the hospital. Malignant peritoneal mesothelioma was diagnosed previously. According to the clinical findings, and laboratory and pathologic examination, the patient was found to have disseminated venous thrombosis and antiphos pholipid syndrome, which is treatment-resistant autoimmune paraneoplastic syndrome.

Effects of DMSO on platelet functions and P-Selectin expression during storage

Recent studies suggested that the expression of P-Selectin on stored platelets is related to in vitro activation and loss of viability. We examined the effects of dimethylsulfoxide (DMSO) on in vitro function and P-Selectin expression of platelet concentrates. Fresh random-donor platelet units (n = 60) were divided into four equal groups. A DMSO-free group was chosen as a control. DMSO (0.5%, 1.0%, and 3.0%) was added to the other three groups. The samples were stored on a horizontal shaker at room temperature. Biochemical, morphological and platelet function tests and P-Selectin expression were monitored during storage. In all groups, P-Selectin expression, lactate and LDH levels, mean platelet volumes and PO2 increased but the aggregation response to agonist, the recovery response to hypotonic shock, platelet count, glucose level, pCO2, and HCO3 decreased during storage. In DMSO-containing groups, the P-Selectin expression which is a predictor of in vitro activation, was found significantly less often than in the DMSO-free group.

Irinotecan plus cisplatin combination against metastatic gastric cancer

In this phase II study, we aimed to detect efficacy and toxicity of the combination of CPT-11 and cisplatin administered to patients with metastatic gastric carcinoma. On d 1, CPT-11, 100 mg/m2, was administered by intravenous infusion for 90 min, followed by a 2 h infusion of cisplatin, at 70 mg/m2 every 3 wk. Forty-one patients were enrolled into the study. Twenty-eight patients were chemotherapy naive. The total number of chemotherapy cycles administered was 165, and the median number of cycles received was 4 (range, 1–8 cycles). The median follow-up time was 12 mo (range, 4–34 mo). There were 4 complete responses (9.7%) and 14 partial responses (34.2%), which result in a response rate of 43.9% (18 of 41 patients). The median time to progression was 8.0 ± 0.8 mo with 56% and 13% of patients progression free at 6 and 12 mo, respectively. The median overall survival was 9.0 ± 1.1 mo, with 68 % and 32% of patients alive at 6 and 12 mo, respectively. Grade 3–4 nausea and vomiting was observed in five patients (12%) and grade 3–4 neutropenia in five patients (12%). Grade 3 infection was observed in only one patient (2%). Grade 2 transient liver dysfunction related to chemotherapy was observed in one patient (2%). Chemotherapy was stopped due to nephrotoxicity in one patient (2%). There was no treatment-related death. In conclusion, administration of CPT-11 and cisplatin in this particular dose every 3 wk is effective and well-tolerated treatment regimen.

The Role of c-erbB-2 Expression on the Survival of Patients with Small-Cell Lung Cancer

The aim of this study was to determine the incidence and role of c-erbB-2 overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males; median age- 56.5 yr, range-34–75) all of whom had adequate tissue specimens available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2 overexpression. Seventy-five of the cases were positive for c-erbB-2, had extensive disease. The median overall survival of patients with SCLC whose tumors were positive and negative for c-erbB-2 were 8 ± 0.9 months (95%CI 6.3–9.7) and 11 ± 1.5 months (95%CI 8.0–14.0), respectively. c-erbB-2 overexpression detected using immunohistochemistry is observed in 17.9% of patients with SCLC and has statistically significant prognostic value. Our findings suggest that c-erbB-2 may be a potential target for site-specific immunotherapy in SCLC. Considering one technique examined, further molecular investigation is needed to confirm these preliminary findings.

Shedding of the nails due to chemotherapy (onychomadesis)

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Ifosfamide, mesna, and interferon-alpha2A combination chemoimmunotherapy in malignant mesothelioma: results of a single center in central anatolia.

Our aim was to determine the efficacy of ifosfamide, mesna, and interferon alpha combination therapy in malignant mesothelioma (MM) patients. Fourty-two patients (39 evaluable) with histologically proven MM were enrolled into this study from January 1999 to October 2002. The drug schedule consisted of a combination of ifosfamide, 3000 mg/m2 1–3 d intravenous infusion (iv), the uroprotective agent mesna, 3000 mg/m2 1–3 d iv every 3 wk, and interferon alpha2a, 4.5 MU subcutaneously (sc) 3 d/wk for 6 mo as first-line chemotherapy. Overall, 140 cycles were administered to the 39 patients (median, 3.5 cycles; range, 1 to 6 cycles). Among the 39 patients, 8 partial remissions (PR) (21%) were observed. Thirteen patients (33%) had stable disease for at least 8 wk and 18 (46%) had progressive disease. Overall survival (OAS) and progression free survival (PFS) for all patients were 10.0 ± 2.9 mo (95%CI 4.3–15.7) and 5.0 ± 1.9 mo (95%CI 1.38–8.62), respectively. One and two year survival rates were calculated as 39% and 5%, respectively. All of the PR patients had the epithelial type of MM. Their survival time was 21.0 ± 5.7 mo (95% CI 9.9–32.1) and significantly longer than that of nonresponders (p=0.0061). The toxicity of the drug combination was mild and well tolerated. There were no treatment-related deaths. Grade 3–4 neutropenia and febrile neutropenia were seen in 10 patients (26%) and 3 patients (8%), respectively. Chemotherapy was stopped in three patients because of renal function deficiency. One of these patients—who had peritoneal MM—required hemodialysis. In conclusion, this combination therapy showed encouraging antitumor activity with modest toxicity.